title: Prostanoids and aldosterone-induced mild experimental hypertension in rats.
abstract: The goal of this study was to determine the role of prostanoids in a new model of mineralocorticoid-dependent hypertension induced by the subcutaneous infusion of aldosterone (1 micrograms/hr) to normal male Sprague-Dawley rats. This regimen caused a mild and gradual increase in systolic pressure over a period of 4 weeks (113 +/- 1 vs. 137 +/- 3 mm Hg) and was associated with an increase in the in vivo formation of prostaglandins I2 and E2 and of thromboxane A2 in the kidney. High sodium intake induced a fall in the urinary levels of prostaglandin E2 and a rise in the arterial pressure of control rats (126 +/- 1 vs. 113 +/- 1 mm Hg) but did not influence aldosterone-induced hypertension. Indomethacin (3.0 mg/kg/day) caused a profound inhibition of the in vivo synthesis of prostaglandin I2 and thromboxane A2 without modifying the renal production of prostaglandin E2. Although indomethacin exerted no effect on aldosterone-induced hypertension in rats fed a normal diet, it caused a further rise in systolic pressure in aldosterone-treated rats fed a high sodium diet (157 +/- 6 vs. 140 +/- 4 mm Hg). The results of this study in a model of aldosterone-induced mild hypertension in the rat indicate that 1) aldosterone exerts a stimulatory effect on the renal synthesis of prostanoid, particularly prostaglandin E2; 2) thromboxane A2 and prostaglandin I2 do not seem to play a role in aldosterone-induced hypertension under conditions of normal dietary salt intake, whereas the role of prostaglandin E2 is unclear; 3) there is enough sodium in a normal diet to allow for the maximal expression of the hypertensive effect of aldosterone; 4) prostaglandin I2 seems to play a significant role in modulating the cardiovascular impact of a high sodium diet in aldosterone-treated rats; and 5) the renal biosynthesis of prostaglandin E2 is particularly resistant to the inhibitory effect of indomethacin in vivo.
authors.affiliation: Laboratory on Prostaglandins, Université de Montréal, Québec, Canada.
authors.forename: R T
authors.initials: RT
authors.lastname: Hui
authors.forename: J H
authors.initials: JH
authors.lastname: Grose
authors.forename: M
authors.initials: M
authors.lastname: Lebel
authors.forename: P
authors.initials: P
authors.lastname: Falardeau
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000450:Aldosterone / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012982:Sodium, Dietary / Q000008:administration & dosage; D013929:Thromboxane B2 / Q000652:urine; D013931:Thromboxanes / Q000502:physiology*
chemical_list: D011453:Prostaglandins; D012982:Sodium, Dietary; D013931:Thromboxanes; D000450:Aldosterone; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D007213:Indomethacin